Promising Phytomedicinals

Two hundred and fifty years ago, there were few or no synthetic medicines. The
250,000-300,000 species of higher plants were the main source of drugs for the
world's population. Today, 75% of the world's population, the poor 3/4ths,
still relies on those plants and other tools of traditional medicine. In the
U.S. and Europe the ecological movement has brought about a renewed interest in
traditional medicines. High inflation rates in the third world have caused
some citizens to return to or begin using herbal remedies. In Bolivia, the
Ministry of Health and the Faculty of Medicine of the National University have
given official and moral support for the return to native medicines (Healy
1986). Life expectancy of the poor has not increased quite so much as with the
richer quarter of the world's population, who depend on non-traditional
medicine. Even among prescription drugs, at least 25% contain at least one
compound derived from higher plants. The percentage might be higher if we
include over-the-counter (OTC) drugs. Today, many avant garde North American
citizens, too, are beginning to seek natural alternatives to iatrogenic
synthetics. The prescription drug market is around $40 billion** today,
suggesting a value of about $10 billion for those drugs containing at least one
compound derived from higher plants. Ironically, illicit drugs, mostly natural
generate more revenue than prescription drugs, United States markets alone for
illicit drugs are estimated at more than $150 billion.

In the 250 years when the "developed" quarter of the world shifted largely from
naturals to synthetics, life expectancy and population nearly doubled,
especially among the "developed" quarter. Who, then, would argue that natural
drugs are better than synthetics? Some advocates of natural medicine tend to
opt for the natural given a choice between a natural and synthetic of equal
efficacy and toxicity. They argue that humans and our hominid ancestors
coevolved with the natural compounds. Our genes and immune system also
coevolved with many of the natural compounds, but have not experienced any of
tomorrow's synthetics.

Table 1 was compiled mostly from published lists (Morton 1977, Farnsworth et
al. 1985, Duke 1985a, and Tyler 1987). It lists 250 of the more important
medicinal species, including those from which many of our prescription drugs
are derived. Though more than half, maybe even more than three quarters, of
the world's plant species are tropical, only about half of these 250 medicinal
species are tropical. Why should half of the medicinal species be temperate?
Simply because developed countries developed most drugs and, with the peculiar
exception of the United States, developed countries tended to study their local
flora first enabling them to rely on their own domestic supply. However, the
United States imports much of its crude drug supply. Because of the high cost
of labor in the United States, it is cheaper to import such things as chamomile
from Europe, psyllium from India, and even jimson weed. But finished
pharmaceutical products, like agricultural products, are among the few
non-deficit columns in the United States export-import balance sheet.

I agree with others, such as Norman Farnsworth, America's most outspoken
pharmacognoscist, who believe that somewhere in the plant kingdom there is a
remedy for everything. But we may have to wait for the Japanese to develop and
promote these remedies. In 1986, Japan developed 40% of the new drugs reaching
the market, while the United States, United Kingdom, Germany, and France all
together came up with only 40%, leaving 20% for the rest of the world. In
1987, Japan captured 56% of the natural product patents summarized in
Phytotherapy Research.

Evolution argues quietly for the natural drug, while economics argues loudly
for the unnatural drug. It now costs $125 million to bring a new drug to
market in the United States. Out of 4,000 starts, only one makes it to market.
Drug companies are not inclined to invest $125 million to prove an herb safe
and efficacious. If we grow our medicine and self-medicate, the drug companies
could not recoup their $125 million. Pharmaceutical firms do actively study
potential medicinal plants, discovering bioactive compounds, which, with some
molecular modifications, become proprietary, enabling them to recoup their
investment

Podophyllotoxin and/or deoxypodophyllotoxin occur in such diverse genera as
Anthriscus, Hernandia,Juniperus, Linum, and Podophyllum,
some temperate, some tropical. Podophyllotoxin has been converted to etoposide
(or vepeside) by a pharmaceutical firm (Bristol Myers). Etoposide was approved
for cancer of the testicles in 1984 and for small cell cancer of the lungs in
1986. We assume, since the drug is approved, that it is safe and efficacious.
It is said to be more safe and efficacious than the natural compound from which
it derives. As with aspirin, etoposide may have fewer side effects than the
natural compound from which it derives. But if the natural compound
podophyllotoxin were safer and/or more efficacious, Bristol Myers would not be
obligated to tell us. They could legally, and with economic good sense,
withhold that information until the patent on etoposide expires. Who knows?
Conceivably they may already have better naturals and semisynthetics! Why
should they introduce them until they've recouped their investment on
etoposide? Drug companies' fiscal health necessarily comes before your
physical health.

All plant species contain poisonous, medicinal and nutritional compounds. For
example, the nutritional value of herb teas is not to be discounted. Almost
any foliar herb tea, with its vitamin C, could have prevented scurvy, scourge
of sailors of the day of long voyages. In the tropics, 25-50 million children
may be suffering from xerophthalmia, which could be alleviated or corrected by
beta-carotene. A single large carrot may provide four times the vitamin A
recommended daily allowance (RDA) (as beta-carotene). Fresh leafy vegetables
average about 4,000 ug beta-carotene per 100 g. Foliar herbs used in herb teas
also contain relatively high levels of betacarotene. On a zero-moisture basis
(ZMB, water removed by calculation), the average herb is richer than 3% milk
(ZMB) in fiber, calcium, iron, vitamin A, thiamin, niacin, and vitamin C (Duke
and Atchley 1986).

We credit our forefathers with the intelligence to have discovered which
species around them were poisonous and which were edible. Yet we sometimes
seem reluctant to credit them with discovering those intermediate properties we
call medicinal activities. Our forefathers discovered many, if not most of the
important medicinal species tabulated herein. Farnsworth et al. (1985)
calculated that 74% of 119 plant-derived drugs were discovered as a result of
chemical studies to isolate the active substances responsible for their
traditional use. In other words, we are indebted to our fore fathers empirical
observations for about 75% of these currently used botanicals. We may expect
new discoveries and uses among these same species, this year, next decade, next
century. Only in this decade did we learn, e.g., about antiretroviral
activities of hypericin, and anticirrhotic activity of colchicine, compounds
rather common in temperate species.

We obtain our berberine, ephedrine (also synthesized), hypericin, papaverine
(also synthesized), podophyllotoxin, sanguinarine, scopolamine, mostly from
temperate species, but, we could get all of them from tropical species. With
greater species diversity in the tropics, it follows that there is also a
greater diversity in biologically active compounds in the tropics.

We've been cautioned by conservationists that tropical species (and their
contained compounds) are jeopardized by habitat destruction. Such habitat
destruction could endanger sources of some of our current medicines (i.e.
Physostigma) and pesticides (i.e. Ryania) in genera confined to
the tropics. The world will benefit from conservation of these species. The
future discovery of new products from unexplored plants is dependent upon such
conservation.

In Table 1, I've attempted to estimate the relative rarity of the medicinal
plant germplasm in the United States. In Column 3 (Germplasm Availability) a Y
(for Yes) indicates that germplasm is readily available, M (for Maybe)
indicates that germplasm is limited, while an N (for No) indicates a perceived
scarcity or nonexistence of public germplasm in the United States. Species
scored M and N should be obtained through germplasm exploration or exchange.

In a computer data base, entitled Father Nature's Farmacy, I am compiling the
surprising array of new medicinal uses for old (and some new) medicinal plants
and the biologically active compounds contained therein. Firmly convinced that
we could reduce the greenhouse effect significantly I urge the use of natural
medicinal and pesticidal compounds (with biomass fuel as a byproduct in lieu of
fossil fuels). Recently, there was near hysteria over traces of daminozide
(Alar) (LD50 8,400 mg/kg orally in rats) in apples which contain several
natural pesticides more toxic than alar. If Americans are going to get
hysterical over traces of relatively non-toxic pesticides and growth regulators
in the food chain, perhaps the much more copious natural pesticides should be
removed from the food chain and put in the pesticide can, leaving the
synthetics in the minds of man rather than the mouths of babes.

Reforestation of 100 million hectares with medicinal, pesticidal, and energy
species, could tie up enough CO2 to halt the increase in CO2, hence retard or
nullify the greenhouse warming (Duke 1985b). Two billion hectares in oil palm
could provide us with enough oil (50 billion barrels) which, transesterified,
could satisfy the world's energy needs renewably. There's much to be said for
growing energy oils in the tropical zone and food oils (less saturated) in the
temperate zone.

Elsewhere, I have detailed hundreds of new medicinal developments, the majority
with old well-known medicinal species, the minority with species like
Castanospermum australe A. Cunn. et Fras for which I find no folk
medicinal data in the literature.

Here are just a few reported new uses for compounds from well-known old
medicinal species: anabasine as antifumitory, artemisinin for malaria,
chymopapain for disc problems, colchicine for cirrhosis, cynarin for choleretic
activity, huperzine for anticholinesterase activity, hypericin for
antiretroviral activity, gammalinolenic acid for atopic eczema, lobeline as an
antifumitory, pilocarpine for xerostomia, polygodiol for antiyeast activity,
psoralen for leukemia, sanguinarine for antiplaque activity, silymarin for
hepatitis, taxol for antitumor activity, tetrahydrocannabinol for glaucoma,
and yohimbine for serotinergic activity.

If forced to name the most important tropical medicinal species, I would
apologetically list, with caveats, the following: Catharanthus, Cephaelis,
Cinchona, Datura, Dioscorea, Erythroxylum, Physostigma (or
Dioclea), Pilocarpus, Psoralea, and Rauwolfia.
Collectively these have played a big role in dozens of major disorders. The
United States is deficient in germplasm for more than half of these.

Once we have investigated and analyzed the tropical species as intensively as
temperate species, I predict we'll find many more important medicinal species
in the tropics. Already there are hundreds of well-known biologically active
compounds from the thousands of tropical species that are used as folk or
proven medicines. But fewer than 2% of these tropical species have been
analyzed. It seems our duty as plant scientists and custodians of Planet Earth
is to study carefully these plants. The value of products they can produce
will exceed by a magnitude or more the cost of preserving them from
extinction.

Somewhere in the tropics, there are probably compounds that will alleviate or
correct every ailment known to mankind. Let's only hope someone finds them
before the species and Tropical Medicine Chest become extinct. The survival of
mankind is intimately dependent on the survival of forests. The more diverse
tropical floras, containing more biologically active compounds, are even more
threatened than the better studied temperate floras.